Chronic Treatment with the 5-HT1A Receptor Partial Agonist Tandospirone Increases Hippocampal Neurogenesis

A large-scale clinical trial, the Sequence Trial Alternatives to Relieve Depression (STAR*D) study, concluded that about one-third of the studied patients with major depressive disorder remitted during the initial treatment with selective serotonin reuptake inhibitors and that approximately half of the remitted subjects relapsed over a 1-year follow-up. The development of new therapeutic approaches with potent efficacy and good tolerability for the treatment of depressive disorders is of great importance. Adult hippocampal neurogenesis has been proposed to be important for understanding and treating depression and anxiety. The present study aimed to elucidate whether or not 5-hydroxytryptamine 1A (5-HT1A) receptor partial agonists have a potential therapeutic effect for the treatment of depressive and anxiety disorders, from the standpoint of neurogenesis.

Male Sprague-Dawley rats were subcutaneously administered a vehicle or tandospirone (TDS) (1 or 10 mg/kg) once daily for 14 days. The effects of chronic TDS treatment on neurogenesis were evaluated on the day after the last injection. The quantification of hippocampal neurogenesis was estimated using immunostaining with doublecortin (DCX), a marker protein of newborn neurons.

Chronic TDS treatment resulted in a significant increase in the number of DCX-positive cells per volume of dentate gyrus in a dose-dependent manner.

The results strongly suggest that 5-HT1A receptor partial agonists would be useful and beneficial in the treatment of depressive and anxiety disorders through increased hippocampal neurogenesis.